Characterization of the role of CD34 in adult skeletal muscle regeneration

• Main Author: Alfaro, Leslie Ann So
• Language: English
• Published: University of British Columbia 2011
• Online Access: http://hdl.handle.net/2429/39344

Expression of the cell surface sialomucin CD34 is common to many adult stem cell types, including muscle satellite cells. However, no clear stem cell or regeneration-related phenotype has ever been reported in mice lacking CD34, and its function on these cells remains poorly understood. Here, we assess the functional role of CD34 on satellite cell-mediated muscle regeneration. Using an optimized flow cytometry-based method to analyze myogenic progenitors, we show that CD34’s expression is tightly regulated early during the muscle regeneration process. Following this, we show that Cd34⁻/⁻ mice, which have no obvious developmental phenotype, display a defect in muscle regeneration when challenged with either acute or chronic muscle injury, resulting in impaired myofibre hypertrophy. In vivo engraftment efficiency and BrdU proliferation assays comparing WT and Cd34⁻/⁻ myogenic progenitors attribute this defect to impaired myogenic progenitor cell function in Cd34⁻/⁻ animals. Lastly, the culture of isolated single myofibres demonstrate that this overall muscle regenerative defect is caused by a delay in the activation of satellite cells lacking CD34 as well as impaired proliferation following activation. Consistent with the reported anti-adhesive function of CD34, Cd34⁻/⁻ satellite cells also show decreased motility along their host myofibre. Altogether, our results identify a role for CD34 in the poorly understood early steps of satellite cell activation, and provide the first evidence that beyond being a stem cell marker, CD34 may play an important function in modulating satellite cell activity. === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate